Differential Gut Microbial Signatures Induced by Exercise Intensity and Mode in Aging SAMP6 Mice

Background: The aging population faces increased risks of metabolic and cognitive decline, with emerging evidence linking gut microbiota to exercise-mediated health benefits. Senescence-accelerated mouse prone 6 (SAMP6) exhibits early aging phenotypes, while senescence-resistant 1 (SAMR1) serves as a healthy control. Methods: Thirty-six male SAMP6 and twelve SAMR1 mice (5- and 7-month-old) were assigned to eight groups (n = 6/group). Seven-month-old SAMP6 mice underwent 8 weeks of treadmill training: low-intensity continuous (12 m/min), moderate-intensity continuous (15 m/min), high-intensity interval training (HIIT; 12/20 m/min), or progressively intensified protocol (12→15 m/min). Fecal samples were collected post-intervention for 16S rRNA sequencing (V3–V4 region). Alpha diversity, beta diversity, and taxonomic composition were analyzed. Gut microbiome health index (GMHI) and microbial dysbiosis index (MDI) were calculated to assess health-associated microbial configuration. Results: Sedentary SAMR1 mice exhibited higher alpha diversity than SAMP6 controls, indicating a link between microbial richness and healthy aging. HIIT significantly restructured gut microbiota composition in SAMP6 mice, characterized by enrichment of Eggerthella lenta and Lactobacillus johnsonii , increased Proteobacteria abundance, and reduced overall alpha diversity. Moderate-intensity continuous training (MICT) enriched Faecalibaculum rodentium with milder compositional shifts. Progressively intensified training resulted in an intermediate microbial phenotype. GMHI was positive in SAMR1 and all exercised SAMP6 groups, with HIIT showing the highest score; sedentary SAMP6 groups exhibited negative GMHI. MDI values were consistent with these health-associated shifts. Conclusions: HIIT is associated with distinct compositional shifts and improved gut microbiome health indices in aging-prone mice, despite reduced alpha diversity. These findings highlight exercise intensity as a critical determinant of gut microbial ecology and support HIIT as a candidate precision exercise strategy for older adults. Future studies employing fecal microbiota transplantation are necessary to test causality.